Identification of Gli1 as a progenitor cell marker for meniscus development and injury repair
Qin, L.; Wei, Y.; Sun, H.; Gui, T.; Yao, L.; Zhong, L.; Yu, W.; Heo, S.-J.; Han, L.; Liu, X. S.; Zhang, Y.; Koyama, E.; Long, F.; Zgonis, M. H.; Mauck, R.; Ahn, J.
Show abstract
Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using Gli1-CreER tdTomato mice, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1+ cells. Normally, the tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh activator right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.
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